Expanded analysis of high-grade astrocytoma with piloid features identifies an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1.

High-grade astrocytoma with piloid features (HGAP) is a recently recognized glioma type whose classification is dependent on its global epigenetic signature. HGAP is characterized by alterations in the mitogen-activated protein kinase (MAPK) pathway, often co-occurring with CDKN2A/B homozygous deletion and/or ATRX mutation. Experience with HGAP is limited and to better understand this tumor type, we evaluated an expanded cohort of patients (n = 144) with these tumors, as defined by DNA methylation array testing, with a subset additionally evaluated by next-generation sequencing (NGS). Among evaluable cases, we confirmed the high prevalence CDKN2A/B homozygous deletion, and/or ATRX mutations/loss in this tumor type, along with a subset showing NF1 alterations. Five of 93 (5.4%) cases sequenced harbored TP53 mutations and RNA fusion analysis identified a single tumor containing an NTRK2 gene fusion, neither of which have been previously reported in HGAP. Clustering analysis revealed the presence of three distinct HGAP subtypes (or groups = g) based on whole-genome DNA methylation patterns, which we provisionally designated as gNF1 (n = 18), g1 (n = 72), and g2 (n = 54) (median ages 43.5 years, 47 years, and 32 years, respectively). Subtype gNF1 is notable for enrichment with patients with Neurofibromatosis Type 1 (33.3%, p = 0.0008), confinement to the posterior fossa, hypermethylation in the NF1 enhancer region, a trend towards decreased progression-free survival (p = 0.0579), RNA processing pathway dysregulation, and elevated non-neoplastic glia and neuron cell content (p < 0.0001 and p < 0.0001, respectively). Overall, our expanded cohort broadens the genetic, epigenetic, and clinical phenotype of HGAP and provides evidence for distinct epigenetic subtypes in this tumor type.

Teratocarcinosarcoma-Like and Adamantinoma-Like Head and Neck Neoplasms Harboring NAB2::STAT6: Unusual Variants of Solitary Fibrous Tumor or Novel Tumor Entities?

The archetypal solitary fibrous tumor (SFT) features fibroblastic cells with varying cellularity without any particular architectural arrangement in a collagenous matrix, with staghorn vessels, CD34 and STAT6 expression, and NAB2::STAT6. To date, this fusion is thought to be specific for SFT. With more routine use of fusion gene panels, the histologic diversity of NAB2::STAT6-positive tumors is increasingly appreciated. Here we present four head and neck tumors harboring NAB2::STAT6 but exhibiting remarkably unusual morphologic features for SFT. All cases were pulled from the authors' consultation files. Immunohistochemistry was performed, along with targeted RNA sequencing in all cases, plus DNA next-generation sequencing on two. The cases arose in the nasal cavity (n = 2), retromolar trigone (n = 1) and parapharynx (n = 1), in patients ranging from 39 to 54 (mean, 44). Both nasal cases were biphasic, with a variably cellular collagenized stroma that resembled SFT but also interspersed malignant epithelial and neuroepithelial nests. One of the nasal cases also exhibited overt rhabdomyoblastic differentiation within both components. The two non-nasal cases were comprised of plump, epithelioid cells that were diffusely positive for pan-cytokeratin. One of these cases had prominent cystic change lined by overtly squamous epithelium. STAT6 immunostaining was positive in all cases, although the epithelial/neuroepithelial nests in the sinonasal cases were negative. All cases were confirmed to harbor NAB2::STAT6 by RNA sequencing. The two sinonasal cases were also found to harbor oncogenic mutations. The presented cases highlight a much broader histologic diversity than previously known for neoplasms with NAB2::STAT6. The biphasic nasal cases closely resemble teratocarcinosarcoma, while the epithelioid, cytokeratin-positive cases could be conceptualized as "adamantinoma-like," to borrow terminology already in use for Ewing sarcomas with complex epithelial differentiation. To identify similar cases, pathologists should have a low threshold for using STAT6 immunohistochemistry on any difficult-to-characterize head and neck tumor.

Perfil Anatomopatológico e Imuno-histoquímico de Gliomas de Pacientes da Região de Maringá-PR / Anatomopathological and Immunohistochemical Profile of Gliomas of Patients in the Region of Maringá-PR / Perfil Anatomopatológico e Inmunohistoquímico de Gliomas en Pacientes la Región de Maringá-PR

Introdução: Os gliomas representam 80% dos tumores do sistema nervoso central. A Organização Mundial da Saúde (OMS) adicionou, em 2016, critérios moleculares na classificação dos gliomas. A fisiopatologia e os fatores de risco desses tumores ainda não são totalmente conhecidos. Objetivo: Realizar uma análise retrospectiva dos laudos anatomopatológicos e imuno-histoquímicos de gliomas. Método: Estudo transversal, retrospectivo e descritivo, a partir de exames anatomopatológicos e imuno-histoquímicos realizados entre janeiro de 2014 e dezembro de 2018 em um laboratório de anatomia patológica na cidade de Maringá-PR. Dos 234 laudos relacionados com o termo glioma, 204 foram selecionados para este estudo. Resultados: Foram encontrados tumores astrocitários, ependimários e oligodendrogliais, sendo que os astrocitomas corresponderam à maioria (86,8% dos casos encontrados). A média de idade ao diagnóstico foi de 51,8 anos e houve maior prevalência desses tumores no sexo masculino. Também foram analisadas mutações detectáveis por imuno-histoquímica como p53 (mutada em 66,7% dos testados), isocitrato desidrogenase (IDH) (28,6% mutados), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) e marcadores diagnósticos como o epithelial membrane antigen (EMA) positivo em todos os ependimomas analisados. Conclusão: É inegável a necessidade de novas pesquisas sobre os gliomas tanto no campo epidemiológico, tendo em vista a nova classificação, quanto no escopo fisiopatológico e clínico, com o objetivo de melhorar o entendimento sobre a patologia e o tratamento dos pacientes

Introduction: Gliomas represent 80% of the central nervous system tumors. World Health Organization (WHO) has added, in 2016, molecular features to the classification of gliomas. The pathophysiology and risk factors of these tumors are not yet fully understood. Objective: Perform a retrospective analysis of immunohistochemical and anatomopathological reports of gliomas. Method: Cross-sectional, retrospective and descriptive study carried out from anatomopathological and immunohistochemical exams made between January 2014 and December 2018 in a pathological anatomy laboratory in the city of Maringá-PR. Of the 234 reports related to the term glioma, 204 were selected for this study. Results: Astrocytic, ependymal and oligodendroglial tumors were found, with astrocytomas accounting for the majority (86.8% of the cases found). Mean age at diagnosis was 51.8 years and the prevalence was higher in men. Furthermore, immunohistochemically detectable mutations were analyzed, such as p53 (mutated in 66.7% of those tested), isocitrate dehydrogenase (IDH) (28.6% mutated), X-linked alpha-thalassemia mental retardation (ATRX) (21.0%) and diagnostic markers such as positive epithelial membrane antigen (EMA) in all analyzed ependymomas. Conclusion: The necessity of further researches on gliomas is undeniable , both epidemiologically considering the new classification and within the clinical and pathophysiological scope in order to improve the understanding of the pathology and the treatment for the patients

Introducción: Los gliomas representan 80% de los tumores del sistema nervioso central. La Organización Mundial de la Salud (OMS) agregó, en 2016, criterios moleculares sobre como clasificar los gliomas. La fisiopatología y los factores de riesgo de estos tumores aún no se comprenden completamente. Objetivo: Realizar un análisis retrospectivo de informes inmunohistoquímicos y anatomopatológicos de gliomas. Método: Estudio transversal, retrospectivo y descriptivo con base em pruebas anatomopatológicas e inmunohistoquímicas realizadas entre enero de 2014 y diciembre de 2018 en un laboratorio de anatomía patológica de la ciudad de Maringá-PR. De los 234 informes relacionados con el término glioma, se seleccionaron 204 para este estudio. Resultados: Se encontraron tumores astrocíticos, ependimarios y oligodendrogliales, siendo los astrocitomas la mayoría (86,8% de los casos encontrados). La edad media al diagnóstico fue de 51,8 años y hubo una mayor prevalencia de estos tumores en el sexo masculino. También se analizaron mutaciones detectables inmunohistoquímicamente, como p53 (mutado en 66,7% de los analizados), isocitrato desidrogenase(IDH) (28,6% mutado), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) y marcadores de diagnóstico como epithelial membrane antigen (EMA) positivo en todos los ependimomas analizados. Conclusión: Es innegable la necesidad de profundizaren las investigaciones sobre los gliomas, tanto en el campo epidemiológico, ante la nueva clasificación, como en el ámbito fisiopatológico y clínico, con el objetivo de mejorar el conocimiento sobre la patología y el tratamiento de los pacientes

The Prevalence of Nondiabetic Renal Diseases in Patients with Diabetes Mellitus in the University Hospital of Ribeirão Preto, São Paulo.

OBJECTIVE: To evaluate the prevalence of nondiabetic renal diseases (NDRDs) in renal biopsies of patients with diabetes mellitus (DM) in the University Hospital of Ribeirão Preto, São Paulo. Research Design and Methods. We conducted a retrospective study including kidney biopsies performed in diabetic patients between 1987 and 2013. We evaluated 79 biopsies during this period. The primary variable was the prevalence of NDRD in patients with DM. The secondary variables were the presence of systemic arterial hypertension (SAH), hematuria, time since diagnosis of DM, serum creatinine, and proteinuria levels. The cases were divided into the following groups: isolated diabetic nephropathy (DN-group I), isolated nondiabetic renal diseases (NDRD-group II), associated NDRD/DN (group III), and associated NDRD+NDRD/DN (group IV). RESULTS: Most of the patients (58.22%) presented only alterations arising from DN. NDRDs were present in 41.77% of the patients. Membranous glomerulonephritis (30.3%) and IgA nephropathy (24.24%) were the most prevalent NDRDs. We found no differences between female and male patients with NDRD when assessing the secondary variables. A time since diagnosis of five years or less revealed a statistical difference (p = 0.0005) in the comparison between the isolated DN (group I) and the NDRD+NDRD/DN (group IV). The other secondary variables were not significant in the comparison of the groups. CONCLUSIONS: We concluded that the prevalence of NDRD is 41.77%. Membranous glomerulonephritis was the most prevalent NDRD in our study. We also conclude that the probability of the presence of NDRD with or without concomitant DN is greater for patients who had biopsies with a time since diagnosis of five years or less. A time since diagnosis of ten years or more does not allow the exclusion of the presence of NDRD.

Anus neoplasm: study of a case series

Anus neoplasm accounts for 2 to 4% of colorectal tumors, being more prevalent around the seventh and the eighth decades. Females are mostly affected, and the ratio is 3:1. Its increased prevalence amongst the population in the past years is probably related to the higher number of people that are affected by sexually transmitted diseases, mainly human papillomavirus (types 16 and 18, mostly) and/or the human immunodeficiency virus. Diagnosis is based on clinical findings and anatomopathological tests. The treatment of choice is radiochemotherapy, and the rescue surgery with abdominoperineal resection is used for recurrence and persistence cases. A retrospective and prospective longitudinal observational study was performed with 11 patients diagnosed with anal neoplasm from 2004 to 2010. Six (54.5%) were females and five (45.5%) were males. The incidence was higher in the sixth decade, at the mean age of 54.45 years. The most frequent histological type observed was the epidermoid carcinoma, and the most frequent cell differentiation type was the moderately differentiated. Chemotharapy associated with radiotherapy was used in 81.9% of the patients, and abdominoperineal resection was necessary as a rescue surgery in 18.2% of the patients. (AU)

Neoplasias do ânus correspondem de 2 a 4% dos tumores de intestino grosso, sendo predominante nas sétima e oitava décadas. A maior prevalência é em gênero feminino, com proporção de 3:1. O aumento da prevalência na população nos últimos anos provavelmente está relacionado ao número maior de pessoas com doenças sexualmente transmissíveis, principalmente o papilomavírus humano (tipos 16 e 18, mais comumente) e/ou o vírus da imunodeficiência humana. O diagnóstico é feito a partir de achados clínicos somados ao exame anatomopatológico. O tratamento de escolha baseia-se na radioquimioterapia, sendo a cirurgia de resgate com amputação abdominoperineal utilizada para casos de recidiva ou persistência. Foi feito um estudo observacional longitudinal retrospectivo e prospectivo, com 11 pacientes diagnosticados com neoplasia anal no período de 2004 a 2010. Seis (54,5%) eram do gênero feminino e 5 (45,5%) do masculino. O pico de incidência foi em sexta década, com média de idade de 54,45 anos. O tipo histológico mais encontrado foi o carcinoma epidermoide (72,7%), sendo o moderadamente diferenciado o mais frequente grau de diferenciação. A quimioterapia associada à radioterapia foi instituída em 81,9% dos pacientes, sendo necessária a cirurgia de amputação abdominoperineal como terapia de resgate em 18,2% dos pacientes. (AU)